Choi JY, etal., Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1090-5.
We examined whether common single nucleotide polymorphisms (SNP) in SULT1A1 (c.779G>A, *14A>G, and *85C>T) and SULT1E1 (IVS1-447C>A, IVS4-1653T>C, and *959G>A) genes influenced the risk and survival of breast cancer. Our study population consisted of 989 histolo
gically confirmed sporadic breast cancer patients and 1,054 controls without history of cancer recruited from three teaching hospitals in Seoul. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression model. In the survival analysis for 529 breast cancer patients with completed treatments, the hazard ratios (HR) were calculated with Cox proportional hazard model. Women with the SULT1E1 *959 GA/AA genotype had a moderately decreased breast cancer risk compared with those with the GG genotypes (OR, 0.8; 95% CI, 0.70-1.00). When the haplotypes were considered, the homozygous *959 AA genotype together with the IVS4-1653 T>C base change (CTA-CCA haplotype) was associated with halved breast cancer risk (OR, 0.5; 95% CI, 0.24-0.88) compared with the wild type CTG-CTG haplotype. No other significant overall association was observed between the SULT1A1 and SULT1E1 SNPs nor haplotypes and breast cancer risk. When stratified by survival, patients with the SULT1E1 IVS4-1653 TC/CC genotypes showed a >3-fold risk of recurrence (HR, 3.2; 95% CI, 1.39-7.48) compared with those with the TT genotype. Moreover, when the haplotypes were considered, the SULT1E1 *959 G>A base change together with the IVS4-1653 T>C base change (CTG-CCA haplotype) was associated with a >4-fold risk of breast cancer (OR, 4.2; 95% CI, 1.15-15.15). These findings suggest that genetic polymorphisms of SULT1E1 are associated with increased risk and a disease free survival of breast cancer in Korean women.
Hirata H, etal., Cancer. 2008 May 1;112(9):1964-73.
BACKGROUND: In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and acti
vation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer. METHODS: DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1. RESULTS: A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35-8.93). CONCLUSIONS: This is the first report on the combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer that suggests a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians.
